ELEVATED PLASMA-FIBRINOGEN - CAUSE OR CONSEQUENCE OF CARDIOVASCULAR-DISEASE

An association between increased plasma fibrinogen and an increased ri sk for myocardial infarction (MI) is well established, but the nature of this association is subject to debate. Our aim was to shed light on the potentially causal nature of this association. We examined whethe r increased plasma fibrinogen, due to a condition that is independent of cardiovascular events, also increases the risk for MI. A case-contr ol study was performed in 139 subjects with a history of MI and 287 co ntrol subjects selected from the Rotterdam Study, a population-based c ohort of 7983 subjects aged 55 years and older. The genotype of the -4 55G/A polymorphism in the fibrinogen beta-gene was determined by polym erase chain reaction. Functional plasma fibrinogen levels were determi ned according to von Clauss. The plasma level of fibrinogen was signif icantly higher in subjects with one or two A alleles compared with sub jects with the GG genotype: 3.8 (95% confidence interval [CI], 3.6 to 3.9) g/L and 3.6 (3.5 to 3.7) g/L, respectively. With increasing plasm a fibrinogen level, the risk for MI increased gradually; a rise in fib rinogen of 1 g/L was associated with a 45% increased risk (odds ratio adjusted for age, sex, and smoking, 1.45; 95% CI, 1.12 to 1.88). There was no association between the genotype of the -455G/A polymorphism a nd the risk for MI. The -455G/A polymorphism is therefore associated w ith increased plasma fibrinogen levels but not with an increased risk for MI. These findings indicate that an increased plasma fibrinogen le vel due to this genetic factor does not increase the risk for MI.